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Protein

Acid-sensing ion channel 3

Gene

Asic3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Generates a biphasic current with a fast inactivating and a slow sustained phase. In sensory neurons is proposed to mediate the pain induced by acidosis that occurs in ischemic, damaged or inflamed tissue. May be involved in hyperalgesia. May play a role in mechanoreception. Heteromeric channel assembly seems to modulate channel properties.5 Publications

Miscellaneous

Potentiated by FMRFamide-related neuropeptides (By similarity). Sensitized and potentiated by NPFF and NPSF. Regulated by lactate and Ca2+. Specifically inhibited by APETx2, a sea anemone toxin. Inhibited by anti-inflammatory drugs like salicylic acid.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei26Potassium ion selectivity and permeability1

GO - Molecular functioni

  • enterobactin transmembrane transporter activity Source: Ensembl
  • ligand-gated sodium channel activity Source: MGI
  • PDZ domain binding Source: RGD

GO - Biological processi

Keywordsi

Molecular functionIon channel, Sodium channel
Biological processIon transport, Sodium transport, Transport
LigandSodium

Enzyme and pathway databases

ReactomeiR-RNO-2672351 Stimuli-sensing channels

Protein family/group databases

TCDBi1.A.6.1.2 the epithelial na(+) channel (enac) family

Names & Taxonomyi

Protein namesi
Recommended name:
Acid-sensing ion channel 3
Short name:
ASIC3
Alternative name(s):
Amiloride-sensitive cation channel 3
Dorsal root ASIC
Short name:
DRASIC
Gene namesi
Name:Asic3
Synonyms:Accn3, Drasic
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 4

Organism-specific databases

RGDi708578 Asic3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 19CytoplasmicSequence analysisAdd BLAST19
Transmembranei20 – 40HelicalSequence analysisAdd BLAST21
Topological domaini41 – 435ExtracellularSequence analysisAdd BLAST395
Transmembranei436 – 456HelicalSequence analysisAdd BLAST21
Topological domaini457 – 533CytoplasmicSequence analysisAdd BLAST77

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi20V → P: No effect on selectivity or channel function. 1 Publication1
Mutagenesisi21F → S: Loss of channel function. 1 Publication1
Mutagenesisi26T → K: Alters selectivity of the channel for sodium. No effect on channel function. 1 Publication1
Mutagenesisi40T → G: Loss of regulation by PKC through PRKCABP; when associated with G-523. 1 Publication1
Mutagenesisi523S → G: Loss of regulation by PKC through PRKCABP; when associated with G-40. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL5757

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001813031 – 533Acid-sensing ion channel 3Add BLAST533

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei40Phosphothreonine; by PKC1 Publication1
Disulfide bondi93 ↔ 187By similarity
Disulfide bondi165 ↔ 172By similarity
Glycosylationi176N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi283 ↔ 372By similarity
Disulfide bondi317 ↔ 368By similarity
Disulfide bondi321 ↔ 366By similarity
Disulfide bondi330 ↔ 352By similarity
Disulfide bondi332 ↔ 344By similarity
Glycosylationi400N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei523Phosphoserine; by PKC1 Publication1

Post-translational modificationi

Phosphorylated by PKA (By similarity). Phosphorylated by PKC. In vitro, PRKCABP/PICK-1 is necessary for PKC phosphorylation and activation of a ASIC3/ACCN3-ASIC2/ASIC2b channel, but does not activate a homomeric ASIC3/ACCN3 channel.By similarity1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiO35240
PRIDEiO35240

PTM databases

iPTMnetiO35240
PhosphoSitePlusiO35240

Expressioni

Tissue specificityi

Expressed in sciatic nerve and dorsal root ganglion (at protein level). Expressed in sensory neurons of dorsal root ganglion. Expressed in Golgi interneurons in the granular layer. Also found in superior cervical ganglia, spinal chord and brain stem.4 Publications

Developmental stagei

Expression is first detected at E15.5. Strongly expressed perinatally.1 Publication

Inductioni

Transcriptionally regulated by the proinflamatory mediators nerve growth factor, serotonin, interleukin-1 and bradykinin. Up-regulation upon tissues inflammation is abolished by anti-inflammatory drugs.3 Publications

Gene expression databases

BgeeiENSRNOG00000008380
GenevisibleiO35240 RN

Interactioni

Subunit structurei

Homotrimer or heterotrimer with other ASIC proteins (By similarity). Interacts with LIN7B, MAGI1 and GOPC (By similarity). Interacts with DLG4 and ASIC2. Interacts with STOM; this regulates channel activity. Homotrimeric ASIC3 and ASIC3-containing heterotrimers interact with the cono-RFamide CNF-Tx1.1, and probably CNF-Tx1.2 and CNF-Tx1.3 (AC P0DL71) (PubMed:28396446).By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • PDZ domain binding Source: RGD

Protein-protein interaction databases

DIPiDIP-35759N
IntActiO35240, 5 interactors
MINTiO35240
STRINGi10116.ENSRNOP00000011300

Chemistry databases

BindingDBiO35240

Structurei

3D structure databases

ProteinModelPortaliO35240
SMRiO35240
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi530 – 533PDZ-bindingBy similarity4

Domaini

The PDZ domain-binding motif is involved in interaction with LIN7A, GOPC and MAGI1/BAIAP1.By similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4294 Eukaryota
ENOG410ZNFK LUCA
GeneTreeiENSGT00760000119120
HOGENOMiHOG000247010
HOVERGENiHBG004150
InParanoidiO35240
KOiK04830
OMAiTRMGQCY
OrthoDBiEOG091G053J
PhylomeDBiO35240
TreeFamiTF330663

Family and domain databases

InterProiView protein in InterPro
IPR001873 ENaC
IPR004724 ENaC_chordates
IPR020903 ENaC_CS
PANTHERiPTHR11690 PTHR11690, 1 hit
PfamiView protein in Pfam
PF00858 ASC, 1 hit
PRINTSiPR01078 AMINACHANNEL
TIGRFAMsiTIGR00859 ENaC, 1 hit
PROSITEiView protein in PROSITE
PS01206 ASC, 1 hit

Sequencei

Sequence statusi: Complete.

O35240-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKPRSGLEEA QRRQASDIRV FASSCTMHGL GHIFGPGGLT LRRGLWATAV
60 70 80 90 100
LLSLAAFLYQ VAERVRYYGE FHHKTTLDER ESHQLTFPAV TLCNINPLRR
110 120 130 140 150
SRLTPNDLHW AGTALLGLDP AEHAAYLRAL GQPPAPPGFM PSPTFDMAQL
160 170 180 190 200
YARAGHSLED MLLDCRYRGQ PCGPENFTVI FTRMGQCYTF NSGAHGAELL
210 220 230 240 250
TTPKGGAGNG LEIMLDVQQE EYLPIWKDME ETPFEVGIRV QIHSQDEPPA
260 270 280 290 300
IDQLGFGAAP GHQTFVSCQQ QQLSFLPPPW GDCNTASLDP DDFDPEPSDP
310 320 330 340 350
LGSPRPRPSP PYSLIGCRLA CESRYVARKC GCRMMHMPGN SPVCSPQQYK
360 370 380 390 400
DCASPALDAM LRKDTCVCPN PCATTRYAKE LSMVRIPSRA SARYLARKYN
410 420 430 440 450
RSESYITENV LVLDIFFEAL NYEAVEQKAA YEVSELLGDI GGQMGLFIGA
460 470 480 490 500
SLLTILEILD YLCEVFQDRV LGYFWNRRSA QKRSGNTLLQ EELNGHRTHV
510 520 530
PHLSLGPRPP TTPCAVTKTL SASHRTCYLV TRL
Length:533
Mass (Da):59,227
Last modified:January 1, 1998 - v1
Checksum:i294B57322C74B3DC
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF013598 mRNA Translation: AAB69328.1
RefSeqiNP_775158.1, NM_173135.1
UniGeneiRn.24225

Genome annotation databases

EnsembliENSRNOT00000011300; ENSRNOP00000011300; ENSRNOG00000008380
GeneIDi286920
KEGGirno:286920

Similar proteinsi

Entry informationi

Entry nameiASIC3_RAT
AccessioniPrimary (citable) accession number: O35240
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: January 1, 1998
Last modified: May 23, 2018
This is version 133 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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